The relationship between ill-health and low social status is one of the most pervasive and robust associations in modern epidemiology, one which is as yet poorly understood. We set up the Whitehall II study in 1985 to investigate the causes of socio-economic differences in health, establishing a cohort of 10,314 white-collar workers who have now been followed for a period of 5-7 years. We have paid particular attention to the role of psycho-social factors such as work characteristics and social support in explaining the socio-economic gradient in health. In one study we have combined extensive psycho-social data with health behaviors and biomedical data. This allows examination of both the interaction between psycho-social and biomedical factors and the pathways by which psycho-social factors may operate to cause disease. The main priority of the study to date has been to establish a comprehensive and accurate exposure database. To ensure this, exposure data have been collected on several occasions and extensive validation and reliability studies undertaken. By using a mean of several exposure measures the risk of misclassification is decreased and hence the power of the study increased. Cross-sectional data have been analyzed to establish possible mechanisms and investigate pathways by studying associations between exposures. The infrastructure for collecting outcome data has been established and initial analysis of outcomes performed using sickness absence data. The aim of the next phase of this study is to continue the follow-up of the cohort and collect further outcome data. This will be achieved by 1) continued collection of sickness absence data; 2) obtaining information from GP's regarding long spells of absence; 3) obtaining death certificates and cancer registrations; and 4) a repeat questionnaire to all 10,314 participants to ensure completeness of outcome data. With additional outcome data we will use our extensive exposure database to explain the socio-economic gradient in health, encompassing both external influences and biomedical mechanisms. The main focus of the analysis will be the role of work stress and social supports and networks both in explaining differences in health between socio-economic groups and individual differences in health. The analysis of these individual differences in health will pay particular attention to women and ethnic minorities.